Methods and devices for delivering and monitoring of tobacco, nicotine, or other substances

ABSTRACT

Methods, systems, and devices are described for providing risk evaluation and mitigation strategies for use with modified risk products or other tobacco products, and in particular, associated with nicotine and tobacco products.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/461,284, titled “METHODS AND DEVICES FOR DELIVERY AND MONITORING OFTOBACCO, NICOTINE, OR OTHER SUBSTANCES,” filed Aug. 15, 2014, which is acontinuation-in-part of U.S. patent application Ser. No. 14/012,952,titled “METHODS AND DEVICES FOR DELIVERY AND MONITORING OF TOBACCO,NICOTINE, OR OTHER SUBSTANCES,” filed Aug. 28, 2013, now U.S. PatentApplication Publication No. 2014-0060552, which claims the benefit ofU.S. Provisional Patent Application No. 61/694,046, titled “METHODS ANDDEVICES FOR DELIVERY AND MONITORING OF TOBACCO, NICOTINE, OR OTHERSUBSTANCES,” filed Aug. 28, 2012, each of which is herein incorporatedby reference in its entirety.

BACKGROUND OF THE INVENTION

The use of tobacco products and the harmful side effects of smokingtobacco and nicotine consumption continue to gain increasing attentionworldwide. As more regulations come into effect regarding smoking in thework place or in public, interest in developing alternative methods ofprotecting public health and providing cessation products and methods isgrowing significantly. As with most new therapies or drugs, the federalgovernment has issued regulations intended to protect the public, withenforcement authority granted to the U.S. Food and Drug Administration(FDA).

SUMMARY OF THE INVENTION

It is generally understood that the mission of the US Food and DrugAdministration (FDA) is to advance the public health by helping to speedthe innovations that make medicines and most foods more effective,safer, and more affordable; and help the public get accurate,science-based information they need to use those medicines and foods toimprove their health.

In June, 2009, The Family Smoking Prevention and Tobacco Control Act wassigned into law, creating “The Center for Tobacco Products”, a tobaccocontrol center within the FDA, having the authority to regulate tobaccoindustry in the U.S., by regulating the content, commercial marketing,sale and distribution of tobacco products within the United States. Thelaw also requires tobacco companies and importers to reveal all productingredients and seek FDA approval for any new tobacco products.

Under its new-found, expanded authority, the FDA now has the ability tocontrol the commercial sale and distribution of traditional tobaccoproducts, including cigarettes, pipe tobacco, and cigars, as well as newtobacco and nicotine related products, including; electronic nicotinevaporizers, (e.g. the electronic cigarette); and products withpotentially modified safety risk relative to cigarettes. These productshave new regulatory pathways associated with them, including thoseproscribed under Section 911 (modified risk tobacco products.)

When considering whether to allow the marketing of modified riskproducts or other novel or new but substantially equivalent tobaccoproducts, FDA must consider the benefit to health of individuals and thepopulation as a whole, including: “the increased or decreased likelihoodthat existing users of tobacco products who would otherwise stop usingsuch products will switch to the tobacco product that is the subject ofthe application; the increased or decreased likelihood that persons whodo not use tobacco products will start using the tobacco product that isthe subject of the application; and the risks and benefits to personsfrom the use of the tobacco product that is the subject of theapplication as compared to the use of products for smoking cessationapproved under chapter V to treat nicotine dependence.”

One potential approach for FDA to address the benefits to health ofindividuals and the population could be to require Risk Evaluation andMitigation Strategies (REMS) be put in place for modified risk productsor other tobacco products as a prerequisite for marketing approval.

There are essentially three components to a REMS program: 1. Amedication guide or patient insert; 2. A communication plan forhealthcare providers; and 3. Elements to assure safe use, (ELASU). Adrug's REMS program may not require the provision of all threecomponents, as the specific components a REMS program employs will varybased on the severity of the risks, the population likely to be exposed,and other factors. In fact, the most common REMS only require theprovision of a medication guide.

While REMS components are not uniform, some currently do, or in thefuture, may contain new provisions and requirements for physicians andother certified health care providers. For REMS requiring ETASU,clinicians may be required to: Obtain and dispense drugs throughspecific distribution channels; Possess specific training, education,experience, or certification(s) in order to prescribe these drugs;Enroll patients in registry programs; and, Issue mandatory,time-sensitive reports of patient responses to treatment.

It is possible that one's ability to prescribe and dispense certainmedications, even some that have been on the market for years, could becontingent upon compliance with these REMS provisions.

Applicant has developed novel methods and devices for the delivery andmonitoring of tobacco, nicotine and other substances that will meet orexceed any potential federal regulation in this field.

Provided herein is a method of protecting public health comprising:increasing the likelihood that a first subject or a second subject willstop using a tobacco product by providing a modified risk product orother tobacco product for administration to the first subject addictedto the tobacco product wherein the first subject has previously failednicotine replacement therapy.

In some embodiments the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments the previously failed nicotine replacement therapycomprises abstinence, nicotine gum, nicotine oral spray, nicotineinhaler, nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

In some embodiments, the product is prescribed, provided, or a subject'seligibility is verified by a physician, a nurse, a pharmacist, anaccredited healthcare provider, or an employee of a convenience orretail store.

In some embodiments, the product is prescribed, provided, or a subject'seligibility is verified by an internet or wireless based application,service or business, or by a call center or phone based applicationservice or business.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine, nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples, taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference between saidsamples for nicotine levels, CO levels, or other biomarker levels inblood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

Provided herein is a method of protecting public health comprising:increasing the likelihood that a first subject or a second subject willstop using a tobacco product by providing a modified risk product orother tobacco product for administration to the first subject addictedto the tobacco product only after at least one failed attempt by thefirst subject to quit using such tobacco product. In general, modifiedrisk products or other tobacco products may include tobacco and/ornicotine delivery devices including, for example: an electroniccigarette, an electronic pipe, an electronic cigar, an electronic waterpipe, an electronic vaporizer, and/or a tobacco or nicotine product,used in combination with a risk evaluation and mitigation strategy andmay involve subject eligibility verification, subject complianceverification to a risk mitigation strategy and overall validation of thesuccess of said risk evaluation and mitigation strategy.

In some embodiments, the previously failed at least one attempt to quitusing said tobacco product comprises, abstinence, nicotine gum, nicotineoral spray, nicotine inhaler, nicotine nasal spray, nicotine lozenge,nicotine dermal patch, Bupropion®, Chantix®, or comparable oral nicotinereplacement product.

In some embodiments, the product is prescribed, provided, administered,or subject eligibility verified by a physician, a nurse, a pharmacist,or an accredited healthcare provider, or an employee of a convenience orretail store.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine or nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, CO levels, or other biomarker levels inblood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

Provided herein is a method of protecting public health comprisingincreasing the likelihood that a first subject or a second subject willstop using a tobacco product by providing a modified risk product orother tobacco product for administration to the first subject addictedto the tobacco product only after the modified risk product or othertobacco product is prescribed to the first subject.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine or nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the product is prescribed by a physician, a nurse,a pharmacist, or an accredited healthcare provider.

In some embodiments, the risk evaluation and mitigation strategyincorporates a means of subject compliance verification.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, CO levels, or other biomarker levels inblood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

Provided herein is a method of protecting public health comprisingdecreasing the likelihood that a second subject not using a tobaccoproduct will start using the tobacco product by providing a modifiedrisk product or other tobacco product for administration to the firstsubject addicted to the tobacco product wherein the first subject haspreviously failed nicotine replacement therapy.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the previously failed attempt to quit using saidtobacco product comprises, abstinence, nicotine gum, nicotine oralspray, nicotine inhaler, nicotine nasal spray, nicotine lozenge,nicotine dermal patch, Bupropion, Chantix, or comparable oral nicotinereplacement product.

In some embodiments, the product is prescribed, provided or subjecteligibility verified by a physician, a nurse, a pharmacist, or anaccredited healthcare provider.

In some embodiments, the product is provided or subject eligibilityverified by an employee of a convenience or retail store.

In some embodiments, the product is provided, or subject eligibilityverified by an internet based application, service or business.

In some embodiments, the product is provided or subject eligibilityverified by a call center or phone based application service orbusiness.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine, nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, CO levels, or other biomarker levels inblood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

Provided herein is a method of protecting public health comprisingdecreasing the likelihood that a second subject not using a tobaccoproduct will start using the tobacco product by providing a modifiedrisk product or other tobacco product for administration to the firstsubject addicted to the tobacco product only after at least one failedattempt by the first subject to quit using such tobacco product.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the previously failed attempt to quit using saidtobacco product comprises, abstinence, nicotine gum, nicotine oralspray, nicotine inhaler, nicotine nasal spray, nicotine lozenge,nicotine dermal patch, Bupropion®, Chantix®, or comparable oral nicotinereplacement product.

In some embodiments, the product is prescribed, provided or subjecteligibility verified by a physician, a nurse, a pharmacist, or anaccredited healthcare provider.

In some embodiments, the product is provided or subject eligibilityverified by or an employee of a convenience or retail store.

In some embodiments, the product is provided, or subject eligibilityverified by an internet based application, service or business.

In some embodiments, the product is provided or subject eligibilityverified by a call center or phone based application service orbusiness.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine or nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, CO levels, or other biomarker levels inblood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

Provided herein is a method of protecting public health comprisingdecreasing the likelihood that a second subject not using a tobaccoproduct will start using the tobacco product or an alternative tobaccoproduct, by providing a modified risk product or other tobacco productfor administration to the first subject addicted to the tobacco product,only after the modified risk product or other tobacco product isprescribed to the first subject.

In some embodiments, said modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the product is prescribed by and subjecteligibility verified by a physician, a nurse, a pharmacist, or anaccredited healthcare provider.

In some embodiments, the product is provided or subject eligibilityverified by or an employee of a convenience or retail store.

In some embodiments, the product is provided, or subject eligibilityverified by an internet based application, service or business.

In some embodiments, the product is provided or subject eligibilityverified by a call center or phone based application service orbusiness.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine or nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, CO levels, or other biomarker levels inblood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

Provided herein is a method of treating a first subject addicted to atobacco product, the method comprising administering to the firstsubject who has previously failed nicotine replacement therapy, amodified risk product.

In some embodiments the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments the previously failed nicotine replacement therapycomprises abstinence, nicotine gum, nicotine oral spray, nicotineinhaler, nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

In some embodiments, the product is administered by a physician, anurse, a pharmacist, or an accredited healthcare provider.

In some embodiments, the product is administered by an employee of aconvenience or retail store.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine or nicotine by-product levels, CO levels, or otherbiomarker levels are above or consistent with levels expected for atobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in blood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the subject compliance verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels inexpelled breath samples, measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in saliva samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels in hairsamples, and measuring nicotine levels, nicotine levels, CO levels, orother biomarker levels in urine samples.

In some embodiments, the subject compliance verification is performed bya physician, a nurse, a pharmacist, or an accredited healthcareprovider.

In some embodiments, the subject compliance verification is performed byor an employee of a convenience or retail store.

Provided herein is a method of treating a first subject addicted to atobacco product, the method comprising administering to the firstsubject a modified risk product or other tobacco product only after atleast one failed attempt by the first subject to quit using such tobaccoproduct.

In some embodiments the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments the previously failed nicotine replacement therapycomprises abstinence, nicotine gum, nicotine oral spray, nicotineinhaler, nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

In some embodiments, the product is administered by a physician, anurse, a pharmacist, or an accredited healthcare provider.

In some embodiments, the product is administered by an employee of aconvenience or retail store.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, in expelled breathsamples, in saliva samples, in hair samples, and in urine samples toverify that the subject's nicotine or nicotine by-product levels,nicotine levels, CO levels, or other biomarker levels are above orconsistent with levels expected for a tobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in blood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the subject compliance verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels inexpelled breath samples, measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in saliva samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels in hairsamples, and measuring nicotine levels, nicotine levels, CO levels, orother biomarker levels in urine samples.

In some embodiments, the subject compliance verification is performed bya physician, a nurse, a pharmacist, or an accredited healthcareprovider.

In some embodiments, the subject compliance verification is performed byan employee of a convenience or retail store.

Provided herein is a method of treating a first subject addicted to atobacco product, the method comprising administering a modified riskproduct or other tobacco product to the first subject only after themodified risk product or other tobacco product is prescribed to thefirst subject.

In some embodiments, said modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the modified risk product or other tobacco productis prescribed and administered by a physician, a nurse, a pharmacist, oran accredited healthcare provider.

In some embodiments, the product is administered by an accreditedemployee of a convenience or retail store, or an employee of anaccredited convenience or retail store.

In some embodiments, the product is administered by an internet orwireless based application, service or business.

In some embodiments, the product is administered by a call center orphone based application service or business.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, in expelled breathsamples, in saliva samples, in hair samples, and in urine samples toverify that the subject's nicotine or nicotine by-product levels,nicotine levels, CO levels, or other biomarker levels are above orconsistent with levels expected for a tobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product, for analysis to anaccredited testing facility, and measuring the difference betweensamples for nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in blood, expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the subject compliance verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood, expelled breath, saliva,hair, and/or urine.

In some embodiments, the subject compliance verification is performed bya physician, a nurse, a pharmacist, or an accredited healthcareprovider.

In some embodiments, the subject compliance verification is performed byan employee of a convenience or retail store.

Provided herein is a method for increasing the likelihood that the firstsubject or a second subject will stop using the tobacco product.

Provided herein is a method for decreasing the likelihood that a secondsubject not using the tobacco product will start using the tobaccoproduct.

Provided herein is a method for verifying the at least one prior failedattempt to stop using tobacco products prior to the modified riskproduct or other tobacco product being provided to a first subject.

In some embodiments, the verification comprises collecting samples andmeasuring nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in blood samples, in expelled breath samples, in salivasamples, in hair samples, and in urine samples to verify that thesubject's nicotine or nicotine by-product levels, nicotine levels, COlevels, or other biomarker levels are above or consistent with levelsexpected for a tobacco or nicotine user after verification that thesubject had previously attempted to stop using tobacco products.

In some embodiments, the previously failed attempt may have comprisedusing abstinence, nicotine gum, nicotine oral spray, nicotine inhaler,nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

Provided herein is a method for verifying that a first subject meets atleast one eligibility requirement for use of a modified tobacco riskproduct.

Provided herein is a method for verifying a subject's eligibilityrequirement comprising: possession of an eligibility card, meetingqualifications for the eligibility card, possessing a valid verificationcode, possessing a physician-provided eligibility record, possessing apharmacist-provided eligibility record, and passing apharmacist-provided eligibility evaluation.

In some embodiments of a method having an eligibility requirement, theidentity verification step comprises at least one of:

evidence of meeting a minimum age requirement,

evidence of a previously failed nicotine replacement therapy, and

evidence of a at least one failed attempt by the patient to quit usingsuch tobacco product,

electronic or telephonic verification of a unique subject eligibilitycard or code identifier,

software verification of a unique subject eligibility card or codeidentifier,

electronic fingerprint verification of an eligible subject,

an activation code, or

an electronic dongle, electronic security key fob, or equivalent.

Provided herein is a method for verifying a subject's eligibilityrequirement wherein the verifying step is performed by a physician, anurse, a pharmacist, an accredited healthcare provider an accreditedemployee of a convenience or retail store, or an employee of anaccredited convenience or retail store.

Provided herein is a method for providing a prescription for a modifiedrisk product, wherein said prescription is provided by a qualifiedhealthcare provider.

In some embodiments, said modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

Provided herein is a method of verifying eligibility of a first subjectaddicted to a tobacco product, to be provided with a modified riskproduct, the method comprising, measuring nicotine levels, nicotinelevels, CO levels, or other biomarker levels present in the system of afirst subject prior to administration of said modified risk product orother tobacco product and confirming that said nicotine levels, nicotinelevels, CO levels, or other biomarker levels are above or consistentwith those of a tobacco or nicotine product user.

In some embodiments the method of verifying eligibility comprises;measuring nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in blood samples, expelled breath samples, salivasamples, hair samples, and urine samples.

Provided herein is a method of monitoring compliance of a first subjectaddicted to a tobacco product and participating in a REMS programcomprising a modified risk product, the method comprising, measuringnicotine levels, nicotine levels, CO levels, or other biomarker levelsof a first subject prior to administration of said modified risk productor other tobacco product and measurement of nicotine levels, nicotinelevels, CO levels, or other biomarker levels after administration ofsaid modified risk product, and comparing said prior nicotine priorlevels, nicotine levels, CO levels, or other biomarker levels toanticipated nicotine levels, nicotine levels, CO levels, or otherbiomarker levels after administration of said modified risk product.

In some embodiments, a method of monitoring comprises; using anelectronic signature to track the pattern of use of a vaporizer,electronic cigarette, or other modified risk product or other tobaccoproduct wherein said product transmits a record of use over a givenperiod of time.

In some embodiments, a record of use comprises levels of nicotineconsumed, times, and dates it was consumed.

In some embodiments, the record of use is stored to a data storagedevice and later downloaded for use by a qualified healthcare provideror REMS monitor or administrator.

In some embodiments, the record of use is transmitted wirelessly to adata storage device and later downloaded for use by a qualifiedhealthcare provider or REMS monitor or administrator.

In some embodiments, the record of use is stored within the device, andlater downloaded for use by a qualified healthcare provider or REMSmonitor.

In some embodiments, the record of use may be wirelessly transmittedfrom a data storage device or a component of the modified risk productor other tobacco product to a remote location for use by a qualifiedhealthcare provider or REMS monitor or administrator.

Provided herein is a method of monitoring the use of a modified riskproduct or other tobacco product by a first subject addicted to atobacco product, the method comprising, requiring an identificationrecognition system be activated before use of a modified risk product orother tobacco product can occur.

In some embodiments, the identification recognition system comprises afingerprint scanner, a lip print scanner, face recognition, a retinalscan, a combination code, an activation code, security key fob, ordongle.

In some embodiments, the identification recognition system comprises anelectronic application for a smartphone, laptop, desktop, or tabletcomputing device, capable of communicating with the modified riskproduct or other tobacco product by a wireless communication system.

In some embodiments, the identification recognition system must bewithin a fixed distance of the modified risk product or other tobaccoproduct for product to continue to work.

In some embodiments, the identification recognition system must bewithin about 5 to 20 feet of the modified risk product.

In some embodiments, the identification recognition system must bewithin 10 feet of the modified risk product.

In some embodiments, the identification recognition system must bewithin 5 feet of the modified risk product.

Provided herein is a method of protecting the public health comprisingincreasing the likelihood that a first subject will stop using a tobaccoproduct by providing a modified risk product or other tobacco productfor administration to the first subject addicted to the tobacco productwherein the modified risk product or other tobacco product provides afaster onset of nicotine delivery, or a higher peak level of nicotinedelivery.

Provided herein is a method of risk mitigation wherein the potentialrisk of misuse or abuse of a modified risk product or other tobaccoproduct is ranked or stratified in comparison to other tobacco products.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is determined by comparing thepharmacokinetic profile of the modified risk product or other tobaccoproduct to nicotine.

In some embodiments the pharmacokinetic profile of the modified riskproduct or other tobacco product is determined by the maximum plasmaconcentration (Cmax) of nicotine, compared to a cigarette.

In some embodiments the pharmacokinetic profile of the modified riskproduct or other tobacco product is determined by the time afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette.

In some embodiments the pharmacokinetic profile of the modified riskproduct or other tobacco product is determined by the rate-of-increaseof nicotine delivery or concentration in the plasma of a subjectcompared to a cigarette.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is determined by comparing the nicotineconcentration of the modified risk product or other tobacco productother nicotine products in the market.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is ranked by ease of access associatedwith the prescriber/administrator.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is ranked by ease of access throughvarious distribution channels.

In some embodiments the modified risk product or other tobacco productcomprises vaporizing tobacco leaves above their pyrolytic temperature.

In some embodiments the modified risk product or other tobacco productcomprises heating tobacco leaves below their pyrolytic temperature.

In some embodiments the modified risk product or other tobacco productcomprises vaporization of a nicotine salt.

In some embodiments the modified risk product or other tobacco productcomprises heating of a nicotine salt below its pyrolytic temperature.

Provided herein is a method of protecting the public health wherein theprovider of a modified risk product or other tobacco product is subjectto a compliance verification system.

In some embodiments, the provider verification is performed by anindependent auditor.

Provided herein is a system for verification of subject eligibility,tracking, and reporting use of a modified risk product or other tobaccoproduct comprising: an electronic cigarette, an electronic pipe, anelectronic cigar, an electronic water pipe, or an electronic vaporizer,comprising a battery, an atomizer, electronic circuitry, a memorystorage device for tracking components of usage activity, a means ofmemory transfer, and a charging circuit, a charger base stationcomprising a memory storage device, a means for receiving data from saidmodified risk product or other tobacco product memory storage device andtransmitting said data to a third party, activation software forrecognition of a specific device, keyed to said charger base, capable ofinterfacing with an external device, wherein said external devicecomprises; a smart phone, computer, electronic fob, electronic dongle,and a wireless communication device, e.g.: Bluetooth device.

In some embodiments, the system is used in combination with a riskevaluation and mitigation strategy.

In some embodiments, the system comprises activation means, forrecognition and verification of a subject to establish user eligibilityprior to use.

In some embodiments, the system is used to verify subject compliance foruse of a modified risk product.

In some embodiments the system comprises a means for validating overallsuccess of the risk mitigation product when used with the riskevaluation and mitigation strategies.

In general, in one embodiment, a method of providing a verification ofeligibility for use or purchase of a tobacco product includes: (1)administering a diagnostic test to a subject; (2) determining whetherthe subject has previously used a tobacco product based upon results ofthe diagnostic test; and (3) providing a verification of eligibility foruse or purchase of a tobacco product if results for the diagnostic testindicate that the subject has previously used a tobacco product.

This and other embodiments can include one or more of the followingfeatures. The step of determining can include determining from a saliva,blood, or urine test for nicotine, cotinine, or nicotine by-products.The step of determining can include determining from a carbon monoxidebreath analysis. The step of determining can include determining if thesubject's breath has a reading of greater than 5 ppm CO which canindicate that the subject previously used a tobacco product. The step ofdetermining can include determining if the subject's breath has areading of greater than 10 ppm which can indicate that the subjectpreviously used a tobacco product. The step of determining can includedetermining whether the subject has consumed a tobacco product withinthe last 24 hours. The step of determining can include determiningwhether the subject has consumed a tobacco product on a regular basis,and the step of providing a verification of eligibility can includeproviding the verification for eligibility only if the subjected hasconsumed the tobacco product on a regular basis. The step of determiningcan include determining whether the subject has previously consumedcombustible tobacco. The step of determining can include determiningwhether the subject has previously consumed tobacco from an electroniccigarette, an electronic pipe, an electronic cigar, an electronic waterpipe, or an electronic vaporizer. Providing the subject with theverification of eligibility can include providing at least one of: aprescription from a physician or accredited healthcare provider, aneligibility card or code identifier, an activation code, an electronicdongle, a listing in a database, or an electronic security key fob.Determining and providing steps can be provided by a physician, nurse,pharmacists, accredited healthcare provider, an employee of aconvenience or retail store, an internet or wireless based application,a service or business, a call center or phone based application, or aservice or business.

In general, in one embodiment, a method of providing a verification ofeligibility for use or purchase of a tobacco product includes: (1)sampling a subject's breath; (2) determining, from the subject's breath,whether the subject has previously used a tobacco product based uponresults of the diagnostic test; and (3) providing the subject with averification of eligibility for use or purchase of a tobacco product ifthe subject has previously used a tobacco product based on thedetermination from the subject's breath.

This and other embodiments can include one or more of the followingfeatures. The step of determining can include determining from a carbonmonoxide breath analysis. The step of determining can includedetermining if the subject's breath has a reading of greater than 5 ppmCO which can indicate that the subject previously used a tobaccoproduct. The step of determining can include determining if thesubject's breath has a reading of greater than 10 ppm which can indicatethat the subject previously used a tobacco product. The step ofdetermining can include determining that the subject has consumed atobacco product within the last 24 hours. The step of determining caninclude determining whether the subject has consumed a tobacco producton a regular basis, and wherein the step of providing a verification ofeligibility can include providing the verification for eligibility onlyif the subjected has consumed tobacco products on a regular basis. Thestep of determining can include determining whether the subject haspreviously consumed combustible tobacco. The step of determining caninclude determining whether the subject has previously consumed tobaccofrom an electronic cigarette, an electronic pipe, an electronic cigar,an electronic water pipe, or an electronic vaporizer, or othernon-combustion tobacco product. Providing the subject with theverification of eligibility can include providing at least one of: aprescription from a physician or accredited healthcare provider, aneligibility card or code identifier, an activation code, an electronicdongle, a listing in a database, or an electronic security key fob.Determining and providing steps can be provided by a physician, nurse,pharmacists, accredited healthcare provider, an employee of aconvenience or retail store, an internet or wireless based application,a service or business, a call center or phone based application, or aservice or business.

In general, in one embodiment, a method of providing a tobacco productincludes: (1) determining whether a subject has previously used atobacco product based on a diagnostic assay performed on the subject;and (2) providing a tobacco product to the subject if the diagnosticassay indicates that the subject has previously used a tobacco product.

This and other embodiments can include one or more of the followingfeatures. The step of determining can include determining at the pointof sale. The step of determining can include performing the diagnosticassay using a sensor on the tobacco product. The step of determining caninclude performing the diagnostic assay. The step of determining caninclude looking up the results of the diagnostic assay in a databaseusing a unique identifier of the subject. The tobacco product caninclude an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, or an electronic vaporizer. The step ofdetermining can include determining whether the subject has previouslyused a tobacco product based on a diagnostic test which can include acarbon monoxide breath analysis. The step of determining can includedetermining whether the subject has previously used a tobacco productbased on a diagnostic test which can include a carbon monoxide breathanalysis, wherein a reading of greater than 5 ppm CO in a breath samplecan indicate that the subject has previously used a tobacco product. Thestep of determining can include determining whether the subject haspreviously used a tobacco product based on a diagnostic test which caninclude a saliva, blood, or urine test for nicotine, cotinine, ornicotine by-products.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1A illustrates a possible configuration of an overall RiskEvaluation and Mitigation Strategy (REMS) where a subject has previouslyused a nicotine replacement therapy;

FIG. 1B illustrates another possible configuration of an overall RiskEvaluation and Mitigation Strategy (REMS) where a subject has not used anicotine replacement therapy;

FIG. 2 illustrates a possible configuration of a REMS component programfor the authorization, verification and program compliance of qualifiedprescribers and dispensers of modified risk products or other tobaccoproducts;

FIG. 3A illustrates a possible configuration of a REMS component programfor the authorization and dispensation of prescriptions for a Modifiedrisk product or other tobacco product or other tobacco product when asubject has previously used a nicotine replacement therapy;

FIG. 3B illustrates a possible configuration of a REMS component programfor the authorization and dispensation of prescriptions for a ModifiedRisk Product or other tobacco product when a subject has previously notused a nicotine replacement therapy;

FIG. 3C illustrates a representative test strip for verification ofnicotine presence in a subject's system;

FIG. 3D illustrates an exemplary carbon monoxide monitor forverification of a subject's prior tobacco use;

FIG. 3E is a table showing exemplary cut-off values for variousbiomarkers such that a subject's measured level of the biomarker abovethe cut-off value indicates eligibility for a modified risk or othertobacco product;

FIG. 4 illustrates a possible configuration of a REMS component programfor the purchase of Modified Risk Products or other tobacco products;

FIG. 5 illustrates a possible configuration of a REMS component programfor User Verification of a Modified Risk Product or other tobaccoproduct;

FIG. 6 illustrates a possible configuration of a REMS component programfor User Verification, Tracking, and Automated Reporting Method of aModified Risk Product or other tobacco product and also illustrates apossible system for verification, tracking, and reporting use of, and orsubject compliance for the use of a Modified Risk Product;

FIG. 7A illustrates a possible configuration of a REMS component programfor User Eligibility for, or User Compliance of, a Modified Risk Productor other tobacco product;

FIG. 7B illustrates a representative test strip for verification ofnicotine presence in a subject's system which could be adapted for usein a REMS program for User Compliance or testing for misuse or abuse ofa Modified Risk Product or other tobacco product.

DETAILED DESCRIPTION OF THE INVENTION

Provided herein are methods of protecting the public health byincreasing the likelihood that a subject addicted to a tobacco productwill stop using a tobacco product wherein the subject has previouslyfailed to stop using a tobacco product by other means.

It should be understood that at a minimum, terms used throughout thisspecification have the following meanings:

Definitions

Abstinence: Abstinence has diverse forms and several potentialdefinitions. Commonly it refers to a temporary or partial refrain fromfood, alcohol, sexual activity, or drugs, such as nicotine in tobaccoproducts. Alternately, it could be used to describe total abstinencewhere something is completely removed from one's lifestyle for a periodof time. As it applies herein, abstinence is generally intended to havethe more common meaning of temporary or partial, self-enforced,restraint from indulgence. However, the term may also imply long-termrestraint, wherein a subject has maintained a sustained abstinence;i.e.: several years, without necessarily having quit using said productsentirely.

Administer/Administration: Is intended to mean that a product or servicehas been provided to a subject. Such service may include performing atest, delivering a prescription, or carrying out/providing averification process.

Fail/Failed/Failure: is intended to mean that a subject has notsucceeded with a previous therapy and returned to previous levels (orgreater levels) of tobacco product use. It is commonly understood intherapy programs that early “failure” is a normal part of trying tostop, and more than one attempt at stopping smoking prior to longer-termsuccess is common. Alternatively it could mean inability to refrain fromtotal or sustained abstinence.

Fail/Failed/Failure: May also mean that a subject continues to use a NRTproduct longer than indicated by the prescribing method or suggesteduse, with or without additional use of a tobacco product in addition tothe NRT product. For example; a subject may continue using a nicotinepatch while continuing to smoke cigarettes, beyond the intended “weaningoff” period.

Initiate: Is intended to mean that a subject has at some point begunusing any tobacco cessation therapy or Nicotine Replacement Therapy(NRT) product.

Modified Risk Product: Is intended to mean a tobacco product that issold, distributed, or marketed under regulatory authority, with a claimto reduce harm or the risk of tobacco related diseases, or a tobaccoproduct that is shown to substantially reduce the overall exposure toharmful substances.

Modified Risk Product: May also mean a tobacco or nicotine deliverydevice or product that is sold, distributed, or marketed underregulatory authority comprising a non-combustion-based, orvaporization-based nicotine delivery mechanism with a lower risk factorfor one or more tobacco related diseases or exposure to one or moreharmful substances, which may be substituted for any other oral,combustion, or vaporization-based nicotine delivery product having ahigher risk factor for one or more tobacco related diseases or exposureto one or more harmful substances.

Prescribe/Prescription: Is intended to mean that a product has beenauthorized for distribution to a subject by order of an accreditedhealthcare provider (a physician); i.e.: by prescription (Rx).

Prescribe: May also mean a commonly available over-the-counter productthat has been recommended by an accredited healthcare provider (aphysician, a nurse, a pharmacist); i.e.: by suggestion the use an OTCproduct, not requiring a Rx, but still requiring verification of a typeto meet local, state, or federal regulation by an accredited individual,at the point of distribution. Alternately a person may self-prescribe anavailable OTC product.

Quit: is intended to mean that a subject has completely stopped using a(tobacco) product; i.e.: total (i.e.: smoking) cessation.

Tobacco product: Is generally intended to mean any product produced fromany genus of Nicotiana plants or nightshade family of plants, or aby-product derived therefrom, comprising nicotine, nicotine salts, ornicotine derivatives, which may produce by-products that can be ingestedutilizing oral, combustion, or vaporization delivery.

Tobacco alternative: May also comprise substitute herbal tobaccoproducts such as corn silk, mint, cinnamon, lemongrass, clover, bugasse,and shisha, among others, comprising nicotine, nicotine salts, ornicotine derivatives, which are often mixed or flavored with variousfruit flavors, energy drink flavors, or other appealing flavors andwhich may produce byproducts that can be ingested utilizing oral,combustion, or vaporization delivery.

Treat: Is generally intended to mean providing an alternate remediationto a tobacco product to a subject. Providing a remediation to act upon asubject by providing an agent intended to be a substitute for a tobaccoproduct.

Treat: May also mean substitution of a first tobacco product with asecond tobacco product, wherein the second product has a preferable riskprofile, i.e.: substitution of a tobacco product which utilizescombustion with a tobacco or nicotine product which does not utilizecombustion or which utilizes vaporization.

Validate/Validation: Is intended to mean a procedure for checking that aproduct, service, or system has met the needs or requirements of thestakeholder(s), and is typically done in the later phases of product,process, or system development to assure that the development andverification procedures for a product, service, or system result in aproduct, service, or system that meets initial requirements,specifications and regulations.

Vapor/vaporize/vaporization: Is intended to mean converting a normallyliquid or solid substance into an aerosol, gaseous or semi-gaseousstate, where it is diffused or suspended in the air; i.e.: haze, mist,or steam. Vaporization is also defined as the process for producing agaseous by-product that is produced from a normally liquid or solidstate material, at a temperature which is below the combustiontemperature of said material.

Verify/verification: Is intended to mean a procedure for checking that aproduct, service, or system complies with a regulation, requirement,specification, or imposed condition; e.g.: has met an initial set ofrequirements, specifications or regulations and typically performed inthe initial or development phases of product, process, or systemdevelopment.

Methods:

Provided herein are methods of protecting the public health byincreasing the likelihood that a subject addicted to a tobacco productwill stop using a tobacco product wherein the subject has previouslyfailed to stop using a tobacco product by other means. Such methods mayinclude the use of controlled Risk Evaluation and Mitigation Strategies(REMS) such as that illustrated in FIGS. 1A & 1B. These REMS may beapplied to drugs, biologics, devices, or combination devices thatinclude any two or more of these things. REMS are intended to answer thequestion: “Do the benefits of the drug, biologic, (and/or device)outweigh the risks?” Some of the factors taken into considerationinclude: Seriousness of the disease or condition to be treated

-   -   Size of the patient population;    -   Expected benefit of the drug or biologic (and/or device);    -   Expected duration of treatment;    -   Seriousness of the known or potential adverse events.

These evaluations are performed not only prior to the approval of a newdrug, biologic, (and/or device), in this case, a modified risk productor other tobacco product device for delivering nicotine, but alsothroughout the entire life cycle of the drug, biologic and/or device.This serves as a means to continuously assess the safety and efficacy ofexisting products based on adverse event reports and results frompost-marketing clinical studies.

For every drug, biologic and/or device approved by the FDA, the risksassociated with its use are communicated through the product packageinsert. In some cases, however, the manufacturer and/or the FDA maydetermine that expanded REMS are necessary to go beyond product labelingin order to manage risks and thereby ensure that the benefits outweighthe risks.

As illustrated in FIGS. 1 & 2, elements of a REMS program for NicotineReplacement Therapy (NRT) may include Elements to Assure Safe Use,(ELASU). A Nicotine REMS program as proposed herein is likely tocomprise several algorithms including:

-   -   1. A Prescriber/Dispenser Authorization Algorithm (FIG. 2):        which may include;        -   Specific personnel authorized by statute to prescribe or            dispense a Modified risk product or other tobacco product        -   A defined Risk Evaluation and Mitigation Strategy for the            specific Modified risk product or other tobacco product        -   An auditing and certification program to verify that            qualified prescribers/dispensers are appropriately trained            and following the REMS protocols for verification and            dispensation of Modified risk products or other tobacco            products    -   2. A Prescription Process and Verification Algorithm (FIGS. 3A &        3B): which may include;        -   A method for verifying that only qualified subjects receive            a Modified risk product or other tobacco product, which may            include one or more of the following:            -   i. evidence of meeting a minimum age requirement;            -   ii. evidence of a previously failed nicotine replacement                therapy;            -   iii. evidence of a at least one failed attempt by the                patient to quit using such tobacco product;            -   iv. collecting samples and measuring nicotine levels,                nicotine levels, CO levels, or other biomarker levels in                blood, expelled breath, saliva, hair, or urine to verify                that the subject's nicotine or nicotine by-product                levels, nicotine levels, CO levels, or other biomarker                levels are above or consistent with levels expected for                a tobacco or nicotine user; (FIG. 3C)            -   v. a prescription from a physician or accredited                healthcare provider;            -   vi. electronic or telephonic verification of a unique                subject eligibility card or code identifier;            -   vii. software verification of a unique subject                eligibility card or code identifier;            -   viii. electronic fingerprint verification of an eligible                subject;            -   ix. an activation code;            -   x. an electronic dongle; and            -   xi. an electronic security key fob, or equivalent.        -   A process for dispensing the Modified risk product or other            tobacco product which may include;            -   i. Directly providing a dispensing modified risk device                and/or a modified risk tobacco/nicotine product            -   ii. Registration in a REMS program    -   3. A User Purchasing Verification Algorithm (FIG. 4): which may        include;        -   A method for verifying that a qualified subject may purchase            a modified risk product or other tobacco product from an            authorized distributor, which may include one or more of the            following:            -   i. evidence of meeting a minimum age requirement;            -   ii. evidence of a previously failed nicotine replacement                therapy;            -   iii. evidence of a at least one failed attempt by the                patient to quit using such tobacco product;            -   iv. collecting samples and measuring nicotine levels,                nicotine levels, CO levels, or other biomarker levels in                blood, expelled breath, saliva, hair, or urine to verify                that the subject's nicotine or nicotine by-product                levels, nicotine levels, CO levels, or other biomarker                levels are above or consistent with levels expected for                a tobacco or nicotine user;            -   v. a prescription from a physician or accredited                healthcare provider;            -   vi. electronic or telephonic verification of a unique                subject eligibility card or code identifier;            -   vii. software verification of a unique subject                eligibility card or code identifier;            -   viii. electronic fingerprint verification of an eligible                subject;            -   ix. an activation code;            -   x. an electronic dongle; and            -   xi. an electronic security key fob, or equivalent.    -   4. A Product User Verification (FIG. 5): which may include;        -   A method or process for verifying a subject is authorized to            use a Modified risk product or other tobacco product before            a product will be activated or function; which may include            one or more of the following:            -   i. software verification;            -   ii. card or code identifier;            -   iii. electronic fingerprint verification of an eligible                subject;            -   iv. lip print verification of an eligible subject;            -   v. a special article of clothing;            -   vi. an activation code;            -   vii. an electronic ring;            -   viii. an electronic dongle; and            -   ix. an electronic security key fob, or equivalent.    -   5. A User Verification and Mitigation Tracking System (FIG. 6):        which may include;        -   A Modified Risk System (100) comprising: one or more of the            following:            -   i. an electronic cigarette; (1)            -   ii. an electronic pipe;            -   iii. an electronic cigar;            -   iv. an electronic water pipe; or            -   v. an electronic vaporizer (1), and also comprising one                or more of the following:                -   1. a battery, an atomizer or cartomizer, electronic                    circuitry, a memory storage device for tracking                    component usage activity, a means of memory                    transfer, and a charging circuit;            -   vi. a charger base station (2) comprising one or more of                the following:                -   1. a memory storage device; a means for receiving                    data and transmitting said data from said modified                    risk product or other tobacco product memory storage                    device to a third party;            -   vii. an identification recognition system;            -   viii. activation software for recognition of a specific                device keyed to said charger base and capable of                interfacing with an external device, wherein said                external device comprises one or more of the following:            -   ix. a smart phone (3); a computer; an electronic fob                (4); an electronic dongle; a ring; an article of                clothing; and a wireless communication device (5).    -   6. A REMS Compliance Program (FIG. 7A): which may include;        -   A method of testing to confirm that a subject is complying            with (and not misusing or abusing) the Modified risk product            or other tobacco product.            -   i. Testing strips, CO level, or other methods of                compliance verification (FIGS. 7B and 3D).

Described herein are methods of: (1) increasing the likelihood that asubject will stop using a tobacco product or tobacco alternative; and(2) decreasing the likelihood that a subject not using a tobacco productwill start using the tobacco product. The methods include providing amodified risk product or other tobacco product, such as a device foradministration of nicotine in a vapor form, if the subject: (1) haspreviously failed a nicotine replacement therapy; (2) had a failedattempt to quit using the tobacco product; (3) has a prescription orother verification mechanism indicating eligibility for purchase or useof the modified risk product or other tobacco product.

Provided herein is a method of protecting public health comprising:increasing the likelihood that a first subject or a second subject willstop using a tobacco product or tobacco alternative product by providinga modified risk product or other tobacco product such as a device foradministration of nicotine in a vapor form to a first subject addictedto the tobacco product wherein the first subject has previously failed anicotine replacement therapy. It is generally understood that there arenumerous recognized therapies intended to reduce the use of tobaccoand/or bring about the cessation of addiction to tobacco products and inparticular, nicotine. These include; abstinence, nicotine gum, nicotineoral spray, nicotine inhaler, nicotine nasal spray, nicotine lozenge,nicotine dermal patch, Bupropion®, Chantix®, or similar medications andoral nicotine replacement products. In many cases, these products ormethods fail. The applicant believes that by combining a REMS programwith their Modified risk product or other tobacco product, the user willbe more likely to switch to a preferred form of nicotine delivery whichhas a preferable risk profile, while also minimizing the risk thatnon-tobacco users will initiate use of the modified risk product orother tobacco product.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a REMS typicallyinvolving one or more of the following components; subject eligibilityverification, subject compliance verification to a risk mitigationstrategy, and overall validation of the success of said risk evaluationand mitigation strategy.

Among the methods included in the REMS are methods wherein the productis prescribed, provided, or a subject's eligibility is verified by aphysician, a nurse, a pharmacist, or an accredited healthcare provider.FIG. 3A illustrates one embodiment of a method wherein the potentialsubject may request a prescription for a controlled product from aqualified, accredited healthcare provider, who verifies that the subjectis qualified to receive said product, prior to issuing a prescription. Asubject may be a current tobacco or nicotine user who may havepreviously tried and failed a nicotine replacement therapy.

Alternatively, the product may be regulated as an over the counter (OTC)or retail product, wherein the subject may self-subscribe and acquirethe product by personally requesting it from a qualified individual,authorized to dispense said product, upon proof or verification ofeligibility to acquire said product, such as proof of a minimum agerequirement, etc. FIG. 3B illustrates another embodiment of a methodwherein the potential subject may request an FDA designated modifiedrisk tobacco product or a tobacco alternative product which may includea non-combustion or vaporization-based delivery of nicotine or tobaccofrom a qualified, accredited healthcare provider, or employee of aconvenience or retail store, who verifies that the subject is qualifiedto receive said product. A subject may be a current tobacco or nicotineuser who may or may not have previously tried and failed a nicotinereplacement therapy. A simple nicotine test strip may be all that isrequired for this verification. Alternately, verification may requiremore complex tests comprising: blood, expelled breath, hair, or urinetaken for analysis.

In some embodiments, the devices and methods of using the modified riskproduct or other tobacco product may be provided by, or subjecteligibility verified by, an accredited employee of a convenience orretail store or by an employee of an accredited convenience or retailstore.

In still other situations, the product is prescribed, provided, and orsubject eligibility verified by an internet or wireless basedapplication, service or business. While in still other situations theproduct may be prescribed, provided, or subject eligibility verified bya call center or phone based application service or business. The use ofSkype or other real time phone and internet services makes theseverification and prescribing services possible.

In any of the preceding examples, the prescribers or providers of themodified risk product or other tobacco product have been qualified todeliver said modified risk product or other tobacco product through aREMS compliance verification program as illustrated in FIG. 2, which istypically administered and controlled by a qualified independent partyhaving full authorization to qualify said providers and/or theiremployees and to audit their internal systems for recordkeeping. Eitherthe facility employing the prescribers or providers or the individualprescribers or providers themselves may be qualified and audited.

In some embodiments, the subject eligibility verification comprisesproviding a prescription from an accredited healthcare provider,verifying a subject's identity, a minimum age for eligibility, orverification of a prior nicotine replacement therapy.

In other embodiments the subject eligibility verification may comprisehaving the subject provide an electronic or telephonic verification of aunique subject eligibility card or code identifier, softwareverification of a unique subject eligibility card or code identifier,electronic fingerprint verification, an activation code, or anelectronic dongle, electronic security key fob, or the equivalent.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, expelled breathsamples, saliva samples, hair samples, and in urine samples to verifythat the subject's nicotine or nicotine by-product levels, nicotinelevels, CO levels, or other biomarker levels are above or consistentwith levels expected for a tobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product or other tobacco product,for analysis to an accredited testing facility, and measuring thedifference between samples for nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood, expelled breath, saliva,hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the risk evaluation and mitigation strategy (REMS)may incorporate a means of subject compliance verification and or thesubject's eligibility to participate in a REMS program and have amodified risk product or other tobacco product prescription. Subjectcompliance is commonly used in clinical drug studies to verify theconcentration levels and patient compliance to protocols, among otherclinical study outcome measures. FIG. 7 illustrates one possibleconfiguration for such a REMS program wherein a subject's eligibility toparticipate in a program is first verified prior to being given aprescription, and the subject may be tested again at a later date todemonstrate program compliance.

In other embodiments, the compliance verification or the REMS programvalidation may comprise measuring maximum plasma concentration (Cmax) ofnicotine, compared to a cigarette, the pharmacokinetic profile of themodified risk product or other tobacco product to determine the timerequired after administration of the product for nicotine to reachmaximum plasma concentration (Tmax), compared to a cigarette, oralternatively, to determine the rate-of-increase of nicotine delivery orconcentration in the plasma of a subject compared to a cigarette.

In still other embodiments, the compliance verification may comprisemeasuring relative potential risk of the modified risk product or othertobacco product by comparing the nicotine concentration of the modifiedrisk product or other tobacco product to other nicotine or tobaccoproducts in the market.

Some aspects of these methods may require physical tests that must beperformed to provide accurate and quantifiable data wherein the subjectmust present themselves to a qualified individual in order for the testto be completed. In some embodiments, the subject complianceverification or the REMS program validation testing is performed by aphysician, a nurse, a pharmacist, a phlebotomist, or an accreditedhealthcare provider and the samples obtained are sent to a qualified labfor analysis.

In other embodiments, subject compliance verification is performed by anaccredited employee of a convenience or retail store, or an employee ofan accredited convenience or retail store. Such compliance tests wouldcomprise verification of subject identity and collection of saliva,hair, urine, or breath samples, which could be forwarded to a qualifiedlab for analysis.

Alternatively, subject compliance or the REMS program validation may bemeasured passively through the use of electronic technology. One suchexample of this is illustrated in FIG. 6. In this example, a device thatis a component of modified risk system, may comprise an electroniccigarette, an electronic pipe, an electronic cigar, an electronic waterpipe, or an electronic vaporizer for delivering a nicotine-containingvapor, comprising a battery, an atomizer, electronic circuitry, a memorystorage device for tracking components of usage activity, a means ofmemory transfer, and a charging circuit, along with a charger basestation comprising a memory storage device, a means for receiving datafrom said component device memory storage device and then having theability to transmit said data to a third party which passively monitorsthe device and indirectly, the subject for compliance based on thetransmitted data.

The component device and the charging base would be configured such thatactivation software would be required for recognition of the specificdevice, keyed to said charger base. This software could be embedded andmatched to each component set in a modified risk product or othertobacco product, and be capable of interfacing with an external device,wherein said external device comprises; a smart phone, computer,electronic fob, electronic dongle and a Bluetooth or wirelesscommunication device, which would need to be within a fixed range foractivation and continued use.

Alternatively, the components could be configured with a programmablecode which must be entered periodically for activation. Still furtherthe components could be hard wired with a timing circuit that requiresperiodic physical contact between the components for activation.

In addition, the transmission of collected data could occur over theinternet via a hardwired or wireless connection through a base computerdevice for analysis and validation by an accredited healthcareprofessional or REMS monitor or administrator.

Provided herein is a method of protecting public health comprising:increasing the likelihood that a first subject or a second subject willstop using a tobacco product by providing a modified risk product orother tobacco product for administration to the first subject addictedto the tobacco product only after at least one failed attempt by thefirst subject to quit using such tobacco product. These modified riskproducts or other tobacco products comprise an electronic cigarette, anelectronic pipe, an electronic cigar, an electronic water pipe, anelectronic vaporizer, and/or a tobacco or nicotine product, used incombination with a risk evaluation and mitigation strategy and mayinvolve subject eligibility verification, subject complianceverification to a risk mitigation strategy and overall validation of thesuccess of said risk evaluation and mitigation strategy.

The previously failed attempt to quit using a tobacco product commonlycomprises abstinence, nicotine gum, nicotine oral spray, nicotineinhaler, nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

In some embodiments of the method, the product is prescribed, provided,administered, or a subject's eligibility is verified by a physician, anurse, a pharmacist, or an accredited healthcare provider, asillustrated in FIG. 3.

In other embodiments, the product, which may be an OTC product, isprovided, administered, or subject eligibility verified by an accreditedemployee of a convenience or retail store. In still other embodiments,the product is provided, administered, or a subject's eligibility isverified by an employee of an accredited convenience or retail store.

In still other embodiments, the product which may be either aprescription or OTC product, is provided, administered, or a subject'seligibility is verified by an internet or wireless based application,service or business. In still other embodiments of the method theproduct is provided, administered, or a subject's eligibility isverified by a call center or phone based application service orbusiness, using Skype or other real time phone and internet services.

In some embodiments, the subject eligibility verification comprisesproviding a prescription from an accredited healthcare provider,verifying a subject's identity, a minimum age for eligibility, orverification of a prior nicotine replacement therapy.

In other embodiments the subject eligibility verification may comprisehaving the subject provide an electronic or telephonic verification of aunique subject eligibility card or code identifier, softwareverification of a unique subject eligibility card or code identifier,electronic fingerprint verification, an activation code, or anelectronic dongle, electronic security key fob, or the equivalent.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, expelled breathsamples, saliva samples, hair samples, and in urine samples to verifythat the subject's nicotine or nicotine by-product levels, nicotinelevels, CO levels, or other biomarker levels are above or consistentwith levels expected for a tobacco or nicotine user.

In some embodiments, the risk evaluation and mitigation strategyincorporates a means of subject compliance verification.

In some embodiments, the subject compliance verification comprisescollecting and sending samples taken before (and/or in some variations,after) being provided a modified risk product or other tobacco product,for analysis to an accredited testing facility, and measuring thedifference between samples for nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood, expelled breath, saliva,hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In other embodiments, the compliance verification may comprise measuringmaximum plasma concentration (Cmax) of nicotine, compared to acigarette, the pharmacokinetic profile of the modified risk product orother tobacco product to determine the time required afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette, or alternatively, todetermine the rate-of-increase of nicotine delivery or concentration inthe plasma of a subject compared to a cigarette.

In still other embodiments, the compliance verification may comprisemeasuring relative potential risk of the modified risk product or othertobacco product by comparing the nicotine concentration of the modifiedrisk product to other nicotine products in the market. Analysis of labresults and statistical analysis of subject outcomes would be performedto provide regular reports to the manufacture(s) and the FDA so thatperiodic evaluation of reports of patient responses to treatment,medication/devices, and revisions to medication guides, may bereassessed.

As mentioned previously, some aspects of these methods may requirephysical tests that must be performed to verify subject compliance orREMS validation wherein the subject must present themself to a qualifiedindividual in order for the test to be completed. In some embodiments,the subject compliance verification or REMS validation testing isperformed by a physician, a nurse, a pharmacist, a phlebotomist, or anaccredited healthcare provider.

In other embodiments, subject compliance verification is performed by anaccredited employee of a convenience or retail store, or an employee ofan accredited convenience or retail store.

Provided herein is a method of protecting public health comprisingincreasing the likelihood that a first subject or a second subject willstop using a tobacco product by providing a modified risk product orother tobacco product for administration to the first subject addictedto the tobacco product, only after the modified risk product or othertobacco product is prescribed to the first subject or the first subjectis otherwise verified as eligible to purchase or use the product.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the product is prescribed by a physician, a nurse,a pharmacist, or an accredited healthcare provider.

In some embodiments, the subject eligibility verification comprisesproviding a prescription from an accredited healthcare provider,verifying a subject's identity, a minimum age for eligibility, orverification of a prior nicotine replacement therapy.

Referring to FIG. 3B, in some embodiments, the subject eligibilityverification includes administering a diagnostic test. For example, thediagnostic test can include collecting samples and measuring nicotine orother by-product of tobacco use, such as cotinine, levels in bloodsamples, expelled breath samples, saliva samples, hair samples, and inurine samples to verify that the subject's nicotine or nicotineby-product levels are above or consistent with levels expected for atobacco or nicotine user. As shown in FIG. 3C, a nicotine or cotininetest can determine whether the subject is positive or negative fortobacco. In some embodiments, a cotinine concentration of greater than 7ng/ml, greater than 8 ng/ml, greater than 10 ng/ml, or greater than 12ng/ml in a subject's saliva can be used to identify a user of tobacco.Likewise, a cotinine concentration of greater than 35 ng/mL, greaterthan 40 ng/mL, greater than 42 ng/mL, or greater than 49 ng/mL in asubject's urine can be used to identify a user of tobacco.

Another example of a diagnostic test for subject eligibilityverification is a breath carbon monoxide (CO) test. The breath carbonmonoxide test can be administered, for example, with a carbon monoxidebreath monitor 20 as shown in FIG. 3D. In some embodiments, the monitorcan be handheld. The carbon monoxide monitor 20 can include a sensor 22,such as an electrochemical gas sensor, and a mouthpiece 28 for thesubject to expel air through. The sensor 22 can be used to detect thecarbon monoxide in parts per million (ppm). In some embodiments, a COconcentration of greater than 5 ppm, greater than 6 ppm, greater than 8ppm, or greater than 10 ppm can be used to identify a user of tobacco,e.g. a user of combustible tobacco. For example, the minimum thresholdlevel can be between 3-5 ppm, between 5-10 ppm, or greater than 10 ppm.In some embodiments, the CO level in a user's blood can be used todetermine whether the user has ingested tobacco. The carbon monoxidetest can advantageously detect CO when someone ingested tobacco within10 hours before the test, such as within 8 hours or within 6 hours.Likewise, the carbon monoxide test can detect when someone has ingestedtobacco regularly such that CO has built up a reservoir in their bloodor lungs. In some embodiments, the carbon monoxide test can be given inthe morning (such as within 4 hours of the subject awaking), as regulartobacco users tend to use tobacco within several hours of waking.Further, the carbon monoxide test can be used to determine whether thesubject is a light or heavy smoker. For example, a reading of between 6and 10 ppm can indicate a light user, and a reading of greater than 10ppm can indicate a heavy user. In some embodiments, eligibilityverification can be provided only for heavy users.

Any of the diagnostic tests described herein can also include amechanism to exclude or select for users who have particular smoking,cardiovascular, or respiratory diseases or conditions, such as asthma orchronic obstructive pulmonary disease (i.e., the eligibilityverification can be negative such that the user cannot obtain themodified risk product). For example, the diagnostic test can include anitric oxide (NO) breath analysis to eliminate or select for thesesubjects.

It is to be understand that additional diagnostic tests can also be usedto determine if the subject is a tobacco user, such as tests forthiocyanate, 4-Aminobiphenyl-hemoglobin adduct, Benzo[a]pyrene-DNAadduct, PAH-albumin adduct, urinary tobacco-specific nitrosoamines,urine hyroxyproline, and/or urine mutagenicity levels in the subject.Exemplary cut-off levels for various diagnostic tests (i.e. a measuredlevel above the cut-off value indicates a tobacco user eligible for useof the modified risk product) are included in FIG. 3E.

In some embodiments, when a diagnostic test is used to determineeligibility verification, the readings can be displayed on the deviceitself. For example, the specific readings (e.g., ppm of CO) can beindicated on a display of the device, such as the display 24 of device20 or an indication of passing the cut-off value (e.g., a particularlight 26 or the word “pass” on the display 24 of the device 20) can beindicated on the monitor or device. In other embodiments, when adiagnostic test is used, the results can be processed by a third party,e.g., the device or readings from the device can be passed onto a thirdparty to determine whether the subject is eligible for the modified riskproduct.

Once the subject is verified as eligible (e.g., based upon the resultsof the diagnostic test or prescription by a physician or healthcareprovider), the verified subject can be provided with evidence ofeligibility for purchase or use of the modified risk product. Forexample, subject may be provided with an electronic or telephonicverification of a unique subject eligibility card or code identifier,software verification of a unique subject eligibility card or codeidentifier, electronic fingerprint verification, an activation code,entry into a database, or an electronic dongle, electronic security keyfob, or the equivalent.

In some embodiments, components of the subject eligibility verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store. Insome embodiments, components of the subject eligibility verification canbe self-administered.

In some embodiments, the risk evaluation and mitigation strategyincorporates a means of subject compliance verification. In someembodiments, the subject compliance verification comprises collectingand sending samples taken before (and/or in some variations, after)being provided a modified risk product, for analysis to an accreditedtesting facility, and measuring the difference between samples fornicotine levels in blood, expelled breath, saliva, hair, and in urine.In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store. Inother embodiments, the compliance verification may comprise measuringmaximum plasma concentration (Cmax) of nicotine, compared to acigarette, the pharmacokinetic profile of the modified risk product orother tobacco product to determine the time required afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette, or alternatively, todetermine the rate-of-increase of nicotine delivery or concentration inthe plasma of a subject compared to a cigarette. In still otherembodiments, the compliance verification may comprise measuring relativepotential risk of the modified risk product or other tobacco product bycomparing the nicotine concentration of the modified risk product orother tobacco product to other nicotine products in the market. Analysisof lab results and statistical analysis of subject outcomes would beperformed to provide regular reports to the manufacture(s) and the FDAso that periodic evaluation of reports of patient responses totreatment, medication/devices, and revisions to medication guides, maybe reassessed.

As mentioned previously, some aspects of these methods may requirephysical tests that must be performed to verify subject compliance orREMS validation wherein the subject must present themself to a qualifiedindividual in order for the test to be completed. In some embodiments,the subject compliance verification or REMS validation testing isperformed by a physician, a nurse, a pharmacist, a phlebotomist, or anaccredited healthcare provider. In other embodiments, subject complianceverification is performed by an employee of a convenience or retailstore.

Referring to FIG. 5, in some embodiments, the device itself can includea diagnostic test for verification eligibility. For example, themodified risk product or other tobacco product can include a CO breathanalysis sensor directly on the device, such as on the mouthpiece of themodified risk product, that only allows use of the device if the user isverified as a user of tobacco (e.g. has a CO level of above a particularamount as described above, including above average values for anon-tobacco user).

Examples of sensors and sensor technologies that may be used may includeelectrochemical and Metal oxide semiconductor (MOS) sensors. Anelectrochemical sensor may produce a current that is related to thetarget gas concentration around a sensor. For example, anelectrochemical cell may be used, to provide a highly accurate andlinear output to carbon monoxide concentration, requiring minimal power,and has a long lifetime (e.g., 5 years or greater). MOS (Metal oxidesemiconductor) are typically low cost, small size and may providesuperior performance. For example, the Figaro TGS5342 electrochemicalsensor is 15 mm diameter, 27.9 mm length, however similar sensors may besmaller. In particular, sensors configured to operate as agating/enabling tool for use of any of the devices (e.g., modified riskproducts or other tobacco products) described herein may be specificallyadapted to sample a patient's breath before they can operate the device.Once the sensor has confirmed that the CO level is above a naïvethreshold (e.g., a threshold of CO levels for non-smokers, and/or thosewho have not used modified risk products or other tobacco productsbefore), the device may be enabled for operation for some amount of time(e.g., seconds, minutes, hours). Other examples of sensors may includeSGX sesnortech (E.g., EC4-2000-CO and MICS-4514 MOS sensors), FigaroTGS3870 MOS sensors, and the like.

Provided herein is a method of protecting public health comprisingdecreasing the likelihood that a second subject not using a tobaccoproduct will start using the tobacco product by providing a modifiedrisk product or other tobacco product for administration to the firstsubject addicted to the tobacco product wherein the first subject haspreviously failed nicotine replacement therapy.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy. In some embodiments, the previously failedattempt to quit using said tobacco product comprises abstinence,nicotine gum, nicotine oral spray, nicotine inhaler, nicotine nasalspray, nicotine lozenge, nicotine dermal patch, Bupropion, Chantix, orcomparable oral nicotine replacement product.

In some embodiments, the product is prescribed by a physician, a nurse,a pharmacist, or an accredited healthcare provider.

In some embodiments, the subject eligibility verification comprisesproviding a prescription from an accredited healthcare provider,verifying a subject's identity, a minimum age for eligibility, and/orverification of a previously failed prior nicotine replacement therapy.

In other embodiments the subject eligibility verification may comprisehaving the subject provide an electronic or telephonic verification of aunique subject eligibility card or code identifier, softwareverification of a unique subject eligibility card or code identifier,electronic fingerprint verification, an activation code, or anelectronic dongle, electronic security key fob, or the equivalent.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, expelled breathsamples, saliva samples, hair samples, and in urine samples to verifythat the subject's nicotine or nicotine by-product levels, nicotinelevels, CO levels, or other biomarker levels are above or consistentwith levels expected for a tobacco or nicotine user.

One such mitigation strategy is illustrated in FIG. 4. As illustratedherein, the subject attempting to purchase or acquire a controlledmodified risk product or other tobacco product would provide some formof qualified proof that verifies they are qualified to obtain saidModified risk product or other tobacco product and participate in theREMS. This purchase verification requirement would typically comprises,a prescription for a controlled substance in addition to a formalverification of subject identity which may comprise a fingerprint,facial recognition, retinal scan, or other biometric identification.Alternatively the identification and verification may comprise havingthe subject providing a code, a dongle, an electronic FOB, or webregistration, to name but a few methods.

In some embodiments, the product is provided or a subject's eligibilityis verified by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, an accredited employee of a convenience or retailstore, or an employee of an accredited convenience or retail store.

In some embodiments, the product is prescribed, provided, or subjecteligibility verified by an internet or wireless based application,service or business, or by a call center or phone based applicationservice or business. The use of Skype or other real time phone andinternet services makes these verification and prescribing servicespossible.

In some embodiments, the subject compliance verification comprisescollecting and sending samples for analysis, taken before (and/or insome variations, after) being provided a modified risk product, andmeasuring the difference between samples for nicotine levels, nicotinelevels, CO levels, or other biomarker levels in blood, expelled breath,saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In other embodiments, the compliance verification may comprise measuringmaximum plasma concentration (Cmax) of nicotine, compared to acigarette, the pharmacokinetic profile of the modified risk product orother tobacco product to determine the time required afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette, or alternatively, todetermine the rate-of-increase of nicotine delivery or concentration inthe plasma of a subject compared to a cigarette.

In still other embodiments, the compliance verification may comprisemeasuring relative potential risk of the modified risk product or othertobacco product by comparing the nicotine concentration of the modifiedrisk product or other tobacco product to other nicotine products in themarket. Analysis of lab results and statistical analysis of subjectoutcomes would be performed to provide regular reports to themanufacture(s) and the FDA so that periodic evaluation of reports ofpatient responses to treatment, medication/devices, and revisions tomedication guides, may be reassessed.

As mentioned previously, some aspects of these methods may requirephysical tests that must be performed to verify subject compliance orREMS validation wherein the subject must present themself to a qualifiedindividual in order for the test to be completed. In some embodiments,the subject compliance verification or REMS validation testing isperformed by a physician, a nurse, a pharmacist, a phlebotomist, or anaccredited healthcare provider.

In other embodiments, subject compliance verification is performed by anaccredited employee of a convenience or retail store, or an employee ofan accredited convenience or retail store.

Provided herein is a method of protecting public health comprisingdecreasing the likelihood that a second subject not using a tobaccoproduct will start using the tobacco product by providing a modifiedrisk product or other tobacco product for administration to the firstsubject addicted to the tobacco product only after at least one failedattempt by the first subject to quit using such tobacco product.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, and overall validation of the success of said riskevaluation and mitigation strategy.

In some embodiments, the previously failed attempt to quit using saidtobacco product comprises abstinence, nicotine gum, nicotine oral spray,nicotine inhaler, nicotine nasal spray, nicotine lozenge, nicotinedermal patch, Bupropion®, Chantix®, or comparable oral nicotinereplacement product.

In some embodiments, the product is prescribed, provided, or subjecteligibility verified by a physician, a nurse, a pharmacist, anaccredited healthcare provider, an accredited employee of a convenienceor retail store, or by an employee of an accredited convenience orretail store.

In some embodiments, the product is prescribed, provided, or subjecteligibility verified by an internet or wireless based application,service or business, or by a call center or phone based applicationservice or business. The use of Skype or other real time phone andinternet services makes these verification and prescribing servicespossible.

In other embodiments, the product, which may be an OTC product, isprovided, administered, or a subject's eligibility is verified by anaccredited employee of a convenience or retail store, or by an employeeof an accredited convenience or retail store.

In still other embodiments, the product which may be either aprescription or OTC product, is provided, administered, or a subject'seligibility is verified by an internet or wireless based application,service or business, or by a call center or phone based applicationservice or business, using Skype or other real time phone and internetservices.

In some embodiments, the subject eligibility verification comprisesproviding a prescription from an accredited healthcare provider,verifying a subject's identity, a minimum age for eligibility, orverification of a prior nicotine replacement therapy.

In other embodiments the subject eligibility verification may comprisehaving the subject provide an electronic or telephonic verification of aunique subject eligibility card or code identifier, softwareverification of a unique subject eligibility card or code identifier,electronic fingerprint verification, an activation code, or anelectronic dongle, electronic security key fob, or the equivalent.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, expelled breathsamples, saliva samples, hair samples, and in urine samples to verifythat the subject's nicotine or nicotine by-product levels, nicotinelevels, CO levels, or other biomarker levels are above or consistentwith levels expected for a tobacco or nicotine user. If a second subjecthas not been using a tobacco product or alternative tobacco productcomprising nicotine, such samples would be negative and disqualify saidsecond subject from obtaining a modified risk under this criteria.

As previously described, another method of decreasing the likelihoodthat a second subject not using a tobacco product, will start using thetobacco product after a first addicted subject is prescribed a modifieduse product after a previously failed attempt to quit, could comprisethe passive use of electronic technology. One such example of this isillustrated in FIG. 5. In this example, a device that is a component ofa modified risk system, may comprise an electronic cigarette, anelectronic pipe, an electronic cigar, an electronic water pipe, anelectronic vaporizer, and/or a tobacco or nicotine product, fordelivering a nicotine-containing vapor, comprising a battery, anatomizer, electronic circuitry, a memory storage device for trackingvarious aspects of component usage activity, a means of memory transfer,and a charging circuit, along with a charger base station comprising amemory storage device, a means for receiving data from said componentdevice memory storage device and comprising the means to transmit saiddata to a third party which passively monitors the device andindirectly, the subject, for compliance to the REMS based on thetransmitted data.

The component device would be configured such that activation softwareacting as a user identification system would be required for recognitionof the specific device, keyed to said charger base. This software couldbe embedded and matched to each component set in a modified riskproduct, and be capable of interfacing with an external device, whereinsaid external device comprises; a smart phone, computer, electronic fob,electronic dongle, a special ring, and/or a Bluetooth or wirelessdevice, which would need to be within a fixed range for activation andcontinued use.

Alternatively, the device could be configured to have a fingerprint orlip print reader on the body or mouthpiece that is matched to the firstsubject.

Alternatively a special ring or wrist band worn on the hand of the firstsubject or other article of jewelry could provide a user identificationsystem and be configured to mate with the device, wherein the devicewill only activate if it is in the immediate proximity of the subject'shand.

In any of the prior examples, the devices could be configured withproximity sensors requiring the subject to be within a fixed distancesuch as 20 feet, or ten feet, or more preferably within five feet orless.

Alternatively, the components could be configured with a programmablecode which must be entered periodically for activation. Still furtherthe components could be hard wired with a timing circuit that requires aminimal period of time between uses for activation.

In addition, the device could be configured as shown in FIG. 6 with abase having hardware and software for the transmission of collected dataas previously described. In this example, the modified risk product orother tobacco product configuration could be used for user verification,user compliance, or even validation of a REMS for a modified riskproduct.

Provided herein is a method of protecting public health comprisingdecreasing the likelihood that that a subject not using a tobaccoproduct will start using the product by providing a modified riskproduct or other tobacco product for administration to the first subjectaddicted to the tobacco product, only after the modified risk product orother tobacco product is prescribed to the first subject or the firstsubject is otherwise verified as eligible to purchase or use theproduct.

In some embodiments, the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the product is prescribed by a physician, a nurse,a pharmacist, or an accredited healthcare provider.

In some embodiments, the subject eligibility verification comprisesproviding a prescription from an accredited healthcare provider,verifying a subject's identity, a minimum age for eligibility, orverification of a prior nicotine replacement therapy.

Once the subject is verified as eligible (e.g., based upon the resultsof the diagnostic test or prescription by a physician or healthcareprovider), the verified subject can be provided with evidence ofeligibility for purchase or use of the modified risk product. Forexample, subject may be provided with an electronic or telephonicverification of a unique subject eligibility card or code identifier,software verification of a unique subject eligibility card or codeidentifier, electronic fingerprint verification, an activation code,entry into a database, or an electronic dongle, electronic security keyfob, or the equivalent.

In some embodiments, components of the subject eligibility verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store. Insome embodiments, components of the subject eligibility verification canbe self-administered.

Referring to FIG. 3B, in some embodiments, the subject eligibilityverification includes administering a diagnostic test. For example, thediagnostic test can include collecting samples and measuring nicotine orother by-product of tobacco use, such as cotinine, levels in bloodsamples, expelled breath samples, saliva samples, hair samples, and inurine samples to verify that the subject's nicotine or nicotineby-product levels are above or consistent with levels expected for atobacco or nicotine user. As shown in FIG. 3C, a nicotine or cotininetest can determine whether the subject is positive or negative fortobacco. In some embodiments, a cotinine concentration of greater than 7ng/ml, greater than 8 ng/ml, greater than 10 ng/ml, or greater than 12ng/ml in a subject's saliva can be used to identify a user of tobacco.Likewise, a cotinine concentration of greater than 35 ng/mL, greaterthan 40 ng/mL, greater than 42 ng/mL, or greater than 49 ng/mL in asubject's urine can be used to identify a user of tobacco.

Another example of a diagnostic test for subject eligibilityverification is a breath carbon monoxide (CO) test. The breath carbonmonoxide test can be administered, for example, with a carbon monoxidebreath monitor 20 as shown in FIG. 3D. In some embodiments, the monitorcan be handheld. The carbon monoxide monitor 20 can include a sensor 22,such as an electrochemical gas sensor, and a mouthpiece 28 for thesubject to expel air through. The sensor 22 can be used to detect thecarbon monoxide in parts per million (ppm). In some embodiments, a COconcentration of greater than 5 ppm, greater than 6 ppm, greater than 8ppm, or greater than 10 ppm can be used to identify a user of tobacco,e.g. a user of combustible tobacco. For example, the minimum thresholdlevel can be between 3-5 ppm, between 5-10 ppm, or greater than 10 ppm.In some embodiments, the CO level in a user's blood can be used todetermine whether the user has ingested tobacco. The carbon monoxidetest can advantageously detect CO when someone ingested tobacco within10 hours before the test, such as within 8 hours or within 6 hours.Likewise, the carbon monoxide test can detect when someone has ingestedtobacco regularly such that CO has built up a reservoir in their bloodor lungs. In some embodiments, the carbon monoxide test can be given inthe morning (such as within 4 hours of the subject awaking), as regulartobacco users tend to use tobacco within several hours of waking.Further, the carbon monoxide test can be used to determine whether thesubject is a light or heavy smoker. For example, a reading of between 6and 10 ppm can indicate a light user, and a reading of greater than 10ppm can indicate a heavy user. In some embodiments, eligibilityverification can be provided only for heavy users.

Any of the diagnostic tests described herein can also include amechanism to exclude or select for users who have particular smoking,cardiovascular, or respiratory diseases or conditions, such as asthma orchronic obstructive pulmonary disease (i.e., the eligibilityverification can be negative such that the user cannot obtain themodified risk product). For example, the diagnostic test can include anitric oxide (NO) breath analysis to eliminate or select for thesesubjects.

It is to be understand that additional diagnostic tests can also be usedto determine if the subject is a tobacco user, such as tests forthiocyanate, 4-Aminobiphenyl-hemoglobin adduct, Benzo[a]pyrene-DNAadduct, PAH-albumin adduct, urinary tobacco-specific nitrosoamines,urine hyroxyproline, and/or urine mutagenicity levels in the subject.Exemplary cut-off levels for various diagnostic tests (i.e. a measuredlevel above the cut-off value indicates a tobacco user eligible for useof the modified risk product) are included in FIG. 3E.

In some embodiments, when a diagnostic test is used to determineeligibility verification, the readings can be displayed on the deviceitself. For example, the specific readings (e.g., ppm of CO) can beindicated on a display of the device, such as the display 24 of device20 or an indication of passing the cut-off value (e.g., a particularlight 26 or the word “pass” on the display 24 of the device 20) can beindicated on the monitor or device. In other embodiments, when adiagnostic test is used, the results can be processed by a third party,e.g., the device or readings from the device can be passed onto a thirdparty to determine whether the subject is eligible for the modified riskproduct.

In some embodiments, the product is administered by physician, a nurse,a pharmacist, an accredited healthcare provider, or an employee of aconvenience or retail store.

In some embodiments, the product is administered by an internet orwireless based application, service or business, or by a call center orphone based application service or business. The use of Skype or otherreal time phone and internet services makes these verification andprescribing services possible

In some embodiments, the risk evaluation and mitigation strategyincorporates a means of subject compliance verification.

In some embodiments, the subject compliance verification comprisescollecting and sending samples for analysis, taken before (and/or insome variations, after) being provided a modified risk product, andmeasuring the difference between samples for nicotine levels in blood,expelled breath, saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In other embodiments, the compliance verification may comprise measuringmaximum plasma concentration (Cmax) of nicotine, compared to acigarette, the pharmacokinetic profile of the modified risk product orother tobacco product to determine the time required afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette, or alternatively, todetermine the rate-of-increase of nicotine delivery or concentration inthe plasma of a subject compared to a cigarette.

In still other embodiments, the compliance verification may comprisemeasuring relative potential risk of the modified risk product or othertobacco product by comparing the nicotine concentration of the modifiedrisk product or other tobacco product to other nicotine products in themarket. Analysis of lab results and statistical analysis of subjectoutcomes would be performed to provide regular reports to themanufacture(s) and the FDA so that periodic evaluation of reports ofpatient responses to treatment, medication/devices, and revisions tomedication guides, may be reassessed.

As mentioned previously, some aspects of these methods may requirephysical tests that must be performed to verify subject compliance orREMS validation wherein the subject must present themself to a qualifiedindividual in order for the test to be completed. In some embodiments,the subject compliance verification or REMS validation testing isperformed by a physician, a nurse, a pharmacist, a phlebotomist, or anaccredited healthcare provider.

In other embodiments, subject compliance verification is performed by anaccredited employee of a convenience or retail store, or an employee ofan accredited convenience or retail store.

In some embodiments, the risk evaluation and mitigation strategyincorporates a passive means of subject compliance verification.

As previously described, a device that is a component of a modified risksystem, may comprise an electronic cigarette, an electronic pipe, anelectronic cigar, an electronic water pipe, an electronic vaporizer,and/or a tobacco or nicotine product, for delivering anicotine-containing vapor, comprising a battery, an atomizer, electroniccircuitry, a memory storage device for tracking various aspects ofcomponent usage activity, a means of memory transfer, and a chargingcircuit, along with a charger base station comprising a memory storagedevice, a means for receiving data from said component device memorystorage device and comprising the means to transmit said data to a thirdparty which monitors the device and indirectly, the subject, forcompliance to the REMS based on the transmitted data.

The component device would be configured such that activation softwareacting as a user identification system would be required for recognitionof the specific device, keyed to said charger base. This software couldbe embedded and matched to each component set in a modified riskproduct, and be capable of interfacing with an external device, whereinsaid external device comprises; a smart phone, computer, electronic fob,electronic dongle, and a Bluetooth or wireless device, which would needto be within a fixed range for activation and continued use.

Alternatively, the device could be configured to have a fingerprint orlip print reader on the body or mouthpiece that is matched to the firstsubject.

Alternatively a special ring or wrist band worn on the hand of the firstsubject or other article of jewelry or clothing could provide a useridentification system and be configured to mate with the device, whereinthe device will only activate if it is in the immediate proximity of thesubject's hand or the subject.

Referring to FIG. 5, in some embodiments, the device itself can includea diagnostic test for verification eligibility. For example, themodified risk product or other tobacco product can include a CO breathanalysis sensor directly on the device, such as on the mouthpiece of themodified risk product, that only allows use of the device if the user isverified as a user of tobacco (e.g. has a CO level of above a particularamount as described above, including above average values for anon-tobacco user).

Examples of sensors and sensor technologies that may be used may includeelectrochemical and Metal oxide semiconductor (MOS) sensors. Anelectrochemical sensor may produce a current that is related to thetarget gas concentration around a sensor. For example, anelectrochemical cell may be used, to provide a highly accurate andlinear output to carbon monoxide concentration, requiring minimal power,and has a long lifetime (e.g., 5 years or greater). MOS (Metal oxidesemiconductor) are typically low cost, small size and may providesuperior performance. For example, the Figaro TGS5342 electrochemicalsensor is 15 mm diameter, 27.9 mm length, however similar sensors may besmaller. In particular, sensors configured to operate as agating/enabling tool for use of any of the devices (e.g., modified riskproducts or other tobacco products) described herein may be specificallyadapted to sample a patient's breath before they can operate the device.Once the sensor has confirmed that the CO level is above a naïvethreshold (e.g., a threshold of CO levels for non-smokers, and/or thosewho have not used modified risk products or other tobacco productsbefore), the device may be enabled for operation for some amount of time(e.g., seconds, minutes, hours). Other examples of sensors may includeSGX sesnortech (E.g., EC4-2000-CO and MICS-4514 MOS sensors), FigaroTGS3870 MOS sensors, and the like.

In any of the prior examples, the devices could be configured withproximity sensors requiring the subject to be within a fixed distancesuch as 20 feet, or ten feet, or more preferably within five feet orless.

Alternatively, the components could be configured with a programmablecode which must be entered periodically for activation. Still furtherthe components could be hard wired with a timing circuit that requires aminimal period of time between uses for activation.

In addition, the device could be configured as shown in FIG. 6 with abase having hardware and software for the transmission of collected dataas previously described.

Provided herein is a method of treating a first subject addicted to atobacco product, the method comprising administering to the firstsubject who has previously failed nicotine replacement therapy, amodified risk product.

In some embodiments the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments the previously failed nicotine replacement therapycomprises abstinence, nicotine gum, nicotine oral spray, nicotineinhaler, nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

In some embodiments, the product is administered by a physician, anurse, a pharmacist, or an accredited healthcare provider.

In some embodiments, the product is administered by or an employee of aconvenience or retail store.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, in expelled breathsamples, in saliva samples, in hair samples, and in urine samples toverify that the subject's nicotine or nicotine by-product levels,nicotine levels, CO levels, or other biomarker levels are above orconsistent with levels expected for a tobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples for analysis, taken before (and/or insome variations, after) being provided a modified risk product, andmeasuring the difference between samples for nicotine levels, nicotinelevels, CO levels, or other biomarker levels in blood, expelled breath,saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the subject compliance verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels inexpelled breath samples, measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in saliva samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels in hairsamples, and measuring nicotine levels, nicotine levels, CO levels, orother biomarker levels in urine samples.

In some embodiments, the subject compliance verification is performed bya physician, a nurse, a pharmacist, or an accredited healthcareprovider.

In some embodiments, the subject compliance verification is performed byor an employee of a convenience or retail store.

Provided herein is a method of treating a first subject addicted to atobacco product, the method comprising administering to the firstsubject a modified risk product or other tobacco product only after atleast one failed attempt by the first subject to quit using such tobaccoproduct.

In some embodiments the modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments the previously failed nicotine replacement therapycomprises abstinence, nicotine gum, nicotine oral spray, nicotineinhaler, nicotine nasal spray, nicotine lozenge, nicotine dermal patch,Bupropion®, Chantix®, or comparable oral nicotine replacement product.

In some embodiments, the product is administered by a physician, anurse, a pharmacist, or an accredited healthcare provider.

In some embodiments, the product is administered by an employee of aconvenience or retail store.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, in expelled breathsamples, in saliva samples, in hair samples, and in urine samples toverify that the subject's nicotine or nicotine by-product levels,nicotine levels, CO levels, or other biomarker levels are above orconsistent with levels expected for a tobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples for analysis, taken before (and/or insome variations, after) being provided a modified risk product, andmeasuring the difference between samples for nicotine levels, nicotinelevels, CO levels, or other biomarker levels in blood, expelled breath,saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the subject compliance verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels inexpelled breath samples, measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in saliva samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels in hairsamples, and measuring nicotine levels, nicotine levels, CO levels, orother biomarker levels in urine samples.

In some embodiments, the subject compliance verification is performed bya physician, a nurse, a pharmacist, or an accredited healthcareprovider.

In some embodiments, the subject compliance verification is performed byan employee of a convenience or retail store.

Provided herein is a method of treating a first subject addicted to atobacco product, the method comprising administering a modified riskproduct or other tobacco product to the first subject only after themodified risk product or other tobacco product is prescribed to thefirst subject.

In some embodiments, said modified risk product or other tobacco productcomprises; an electronic cigarette, an electronic pipe, an electroniccigar, an electronic water pipe, an electronic vaporizer, and/or atobacco or nicotine product, used in combination with a risk evaluationand mitigation strategy and may involve subject eligibilityverification, subject compliance verification to a risk mitigationstrategy and overall validation of the success of said risk evaluationand mitigation strategy.

In some embodiments, the modified risk product or other tobacco productis prescribed and administered by a physician, a nurse, a pharmacist, oran accredited healthcare provider.

In some embodiments, the product is administered by an accreditedemployee of a convenience or retail store, or an employee of anaccredited convenience or retail store.

In some embodiments, the product is administered by an internet orwireless based application, service or business.

In some embodiments, the product is administered by a call center orphone based application service or business.

In some embodiments, the subject eligibility verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, in expelled breathsamples, in saliva samples, in hair samples, and in urine samples toverify that the subject's nicotine or nicotine by-product levels,nicotine levels, CO levels, or other biomarker levels are above orconsistent with levels expected for a tobacco or nicotine user.

In some embodiments, the subject compliance verification comprisescollecting and sending samples for analysis, taken before (and/or insome variations, after) being provided a modified risk product, andmeasuring the difference between samples for nicotine levels, nicotinelevels, CO levels, or other biomarker levels in blood, expelled breath,saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In some embodiments, the subject compliance verification comprisescollecting samples and measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in blood samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels inexpelled breath samples, measuring nicotine levels, nicotine levels, COlevels, or other biomarker levels in saliva samples, measuring nicotinelevels, nicotine levels, CO levels, or other biomarker levels in hairsamples, and measuring nicotine levels, nicotine levels, CO levels, orother biomarker levels in urine samples.

In some embodiments, the subject compliance verification is performed bya physician, a nurse, a pharmacist, or an accredited healthcareprovider.

In some embodiments, the subject compliance verification is performed byan employee of a convenience or retail store.

Provided herein is a method for increasing the likelihood that the firstsubject or a second subject will stop using the tobacco product.

In some embodiments, the subject compliance verification comprisescollecting and sending samples for analysis, taken before (and/or insome variations, after) being provided a modified risk product, andmeasuring the difference between samples for nicotine levels, nicotinelevels, CO levels, or other biomarker levels in blood, expelled breath,saliva, hair, and in urine.

In some embodiments, components of the subject compliance verificationmay be performed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store.

In other embodiments, the compliance verification may comprise measuringmaximum plasma concentration (Cmax) of nicotine, compared to acigarette, the pharmacokinetic profile of the modified risk product orother tobacco product to determine the time required afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette, or alternatively, todetermine the rate-of-increase of nicotine delivery or concentration inthe plasma of a subject compared to a cigarette.

In still other embodiments, the compliance verification may comprisemeasuring relative potential risk of the modified risk product or othertobacco product by comparing the nicotine concentration of the modifiedrisk product or other tobacco product to other nicotine products in themarket. Analysis of lab results and statistical analysis of subjectoutcomes would be performed to provide regular reports to themanufacture(s) and the FDA so that periodic evaluation of reports ofpatient responses to treatment, medication/devices, and revisions tomedication guides, may be reassessed.

As a result of having performed the compliance verification testing,subjects are more likely to be interested in the outcomes and act onthose results, including increasing the likelihood that the firstsubject or a second subject will stop using the tobacco product.

Provided herein is a method for decreasing the likelihood that a secondsubject not using the tobacco product will start using the tobaccoproduct. FIGS. 4 and 5 are both illustrations of how a second user wouldbe prevented from acquiring and using a modified risk tobacco product,hence, reducing the likelihood of starting to use the tobacco product.

Provided herein is a method for verifying the at least one prior failedattempt to stop using tobacco products prior to the modified riskproduct or other tobacco product being provided to a first subject.

Provided herein is a method for verifying that a first subject meets atleast one eligibility requirement for use of a modified tobacco riskproduct, as illustrated by FIGS. 3A & 3B.

Provided herein is a method for verifying a subject's eligibilityrequirement comprising: possession of an eligibility card, meetingqualifications for the eligibility card, possessing a valid verificationcode, possessing a physician-provided eligibility record, possessing apharmacist-provided eligibility record, passing a pharmacist-providedeligibility evaluation, as illustrated by FIG. 4.

In some embodiments of a method having an eligibility requirement, theidentity verification step comprises at least one of:

-   -   evidence of a minimum age requirement,    -   evidence of a previously failed nicotine replacement therapy,        and    -   evidence of a at least one failed attempt by the patient to quit        using such tobacco product,    -   electronic or telephonic verification of a unique subject        eligibility card or code identifier,    -   software verification of a unique subject eligibility card or        code identifier,    -   electronic fingerprint verification of an eligible subject,    -   an activation code, or    -   an electronic dongle, electronic security key fob, or        equivalent.

Provided herein is a method for verifying a subject's eligibilityrequirement wherein the verifying step is performed by a physician, anurse, a pharmacist, or an accredited healthcare provider.

In some embodiments, the verifying a subject's eligibility requirementis performed by an accredited employee of a convenience or retail store,or by an employee of an accredited convenience or retail store.

In some embodiments, the verifying a subject's eligibility requirementis performed by an internet or wireless based application, service orbusiness.

In some embodiments, the verifying a subject's eligibility requirementis performed by an internet or wireless based application, service orbusiness.

Provided herein is a method for providing a prescription for a modifiedrisk product, wherein said prescription is provided by a qualifiedhealthcare provider.

Provided herein is a method of monitoring compliance of a first subjectaddicted to a tobacco product, and provided with a modified riskproduct, the method comprising, measuring nicotine levels, nicotinelevels, CO levels, or other biomarker levels of a first subject prior toadministration of said modified risk product or other tobacco productand routine measurement after administration of said modified riskproduct, and comparing said prior nicotine levels, nicotine levels, COlevels, or other biomarker levels to anticipated nicotine levels,nicotine levels, CO levels, or other biomarker levels of the firstsubject after administration of said modified risk product.

In some embodiments the method of monitoring compliance comprises;measuring nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in blood samples, measuring nicotine levels, nicotinelevels, CO levels, or other biomarker levels in expelled breath samples,measuring nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in saliva or urine samples, as illustrated in FIG. 7,or measuring nicotine levels, nicotine levels, CO levels, or otherbiomarker levels in hair samples.

Provided herein is a method of monitoring compliance of a first subjectaddicted to a tobacco product, and provided with a modified riskproduct, the method comprising, measuring nicotine levels consumed by afirst subject prior to administration of said modified risk product orother tobacco product and routine measurement of nicotine levelsconsumed after administration of said modified risk product, andcomparing said prior nicotine levels to anticipated nicotine levels ofthe first subject after administration of said modified risk product.Numerous methods can be devised as evidence herein, and furtherillustrated by one example as shown in FIG. 6.

In some embodiments, a method of monitoring comprises; using anelectronic signature to track the pattern of use of a vaporizer,electronic cigarette, or other modified risk product or other tobaccoproduct wherein said product transmits a record of use over a givenperiod of time.

In some embodiments, a record of use comprises levels of nicotineconsumed, times, and dates it was consumed.

In some embodiments, the record of use is stored to a data storagedevice and later downloaded for use by a qualified healthcare provider.

In some embodiments, the record of use is transmitted wirelessly to adata storage device and later downloaded for use by a qualifiedhealthcare provider.

In some embodiments, the record of use is stored within the device, andlater downloaded for use by a qualified healthcare provider.

Provided herein is a method of monitoring the use of a modified riskproduct or other tobacco product by a first subject addicted to atobacco product, the method comprising, requiring an identificationrecognition system be activated before use of a modified risk product orother tobacco product can take place.

In some embodiments, the identification recognition system comprises, afingerprint scanner, a lip print scanner, face recognition, a retinalscan, a combination code, an activation code, security key fob, ordongle.

In some embodiments, the identification recognition system comprises anelectronic application for a smartphone, laptop, desktop, or tabletcomputing device, capable of communicating with the modified riskproduct or other tobacco product by a Bluetooth or wirelesscommunication system.

In some embodiments, the identification recognition system must bewithin a fixed distance of the modified risk product or other tobaccoproduct for product to continue to work.

In some embodiments, the identification recognition system must bewithin 20 feet of the modified risk product.

In some embodiments, the identification recognition system must bewithin 10 feet of the modified risk product.

In some embodiments, the identification recognition system must bewithin 5 feet of the modified risk product.

Provided herein is a method of risk mitigation wherein the potentialrisk of misuse or abuse of a modified risk product or other tobaccoproduct may be present and require a distinct form of compliancemonitoring.

For example, an addicted subject may continue to use the first tobaccoproduct after being provided the modified risk product, thus increasingthe potential risk for one or more tobacco related diseases or exposureto one or more harmful substances.

In some embodiments, monitoring for misuse or abuse of a modified riskproduct or other tobacco product comprises measuring nicotine levelsconsumed by a first subject prior to administration of said modifiedrisk product or other tobacco product and routine measurement ofnicotine levels consumed after administration of said modified riskproduct, and comparing said prior nicotine levels to anticipatednicotine levels of the first subject after administration of saidmodified risk product.

For example, if an investigator suspected that the subject wascontinuing to use cigarettes after receiving a modified risk product,the results of additional nicotine in the subject's system would be arelatively simple calculation. An example of this calculation could be:[Nicotine or cotinine from cigarettes]=[amount measured in blood orsaliva]−[amount reported as dispensed by modified risk device]. It isunderstood that a similar calculation could be derived from anycomparable nicotine/cotinine test regardless of the testing method,provided testing methods were consistent and/or interchangeable.

In some embodiments, multiple compliance verification and trackingsystems could be combined and randomly or non-randomly applied as partof a REMS program. For example, results of a subject's nicotine level,nicotine levels, CO level, or other biomarker level testing could becompared to prior results (FIG. 7), in addition to remotely monitoringtransmitted usage patterns of the modified risk product or other tobaccoproduct (FIG. 6). Upon comparison, a skilled health professional coulddetermine if abuse or misuse is potentially occurring.

Provided herein is a method of protecting the public health comprisingincreasing the likelihood that a first subject or a second subject willstop using a tobacco product by providing a modified risk product orother tobacco product for administration to the first subject addictedto the tobacco product wherein the modified risk product or othertobacco product provides a faster onset of nicotine delivery, or ahigher peak level of nicotine delivery.

Provided herein is a method of risk mitigation wherein the potentialrisk of misuse or abuse of a modified risk product or other tobaccoproduct is ranked or stratified in comparison to other tobacco products.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is determined by comparing thepharmacokinetic profile of the modified risk product or other tobaccoproduct to nicotine.

In some embodiments the pharmacokinetic profile of the modified riskproduct or other tobacco product is determined by the maximum plasmaconcentration (Cmax) of nicotine, compared to a cigarette.

In some embodiments the pharmacokinetic profile of the modified riskproduct or other tobacco product is determined by the time afteradministration of the product for nicotine to reach maximum plasmaconcentration (Tmax), compared to a cigarette.

In some embodiments the pharmacokinetic profile of the modified riskproduct or other tobacco product is determined by the rate-of-increaseof nicotine delivery or concentration in the plasma of a subjectcompared to a cigarette.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is determined by comparing the nicotineconcentration of the modified risk product or other tobacco productother nicotine products in the market.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is ranked by ease of access associatedwith the prescriber/administrator.

In some embodiments, the relative potential risk of the modified riskproduct or other tobacco product is ranked by ease of access throughvarious distribution channels.

In some embodiments the modified risk product or other tobacco productcomprises vaporizing tobacco leaves or finely chopped tobacco belowtheir pyrolytic temperature.

In some embodiments the modified risk product or other tobacco productcomprises heating tobacco leaves or finely chopped tobacco below theirpyrolytic temperature.

In some embodiments the modified risk product or other tobacco productcomprises vaporization of a nicotine salt.

In some embodiments the modified risk product or other tobacco productcomprises heating of a nicotine salt below its pyrolytic temperature.

Provided herein is a method of validating the effectiveness of amodified risk product or other tobacco product used with a RiskEvaluation and Mitigation Strategy comprising: collecting and sending asubject's samples taken before (and/or in some variations, after) beingprovided a modified risk product, for analysis to an accredited testingfacility, measuring the difference between samples for nicotine levels,nicotine levels, CO levels, or other biomarker levels in blood, expelledbreath, saliva, hair, and/or urine, and performing an appropriateanalysis to determine if the modified risk product or other tobaccoproduct met the goals of the Risk Evaluation and Mitigation Strategy.

In some embodiments, components of the validation process may beperformed by a physician, a nurse, a pharmacist, an accreditedhealthcare provider, or an employee of a convenience or retail store oran accredited testing facility.

Provided herein is a method of protecting the public health wherein theprovider of a modified risk product is subject to a complianceverification system.

In some embodiments, the provider verification is performed by anindependent auditor.

Provided herein is a system for verification, tracking, and reportinguse of a modified risk product comprising: an electronic cigarette, anelectronic pipe, an electronic cigar, an electronic water pipe, anelectronic vaporizer, and a tobacco or nicotine product, comprising abattery, an atomizer, electronic circuitry, a memory storage device fortracking components of usage activity, a means of memory transfer, and acharging circuit, a charger base station comprising a memory storagedevice, a means for receiving data from said modified risk productmemory storage device and transmitting said data to a third party,activation software for recognition of a specific device, keyed to saidcharger base, capable of interfacing with an external device, whereinsaid external device comprises; a smart phone, computer, electronic fob,electronic dongle, and a Bluetooth or wireless device.

In some embodiments, the system is used in combination with a riskevaluation and mitigation strategy.

In some embodiments, the system comprises activation means, forrecognition and verification of a subject to establish user eligibilityprior to use.

In some embodiments, the system comprises activation means, forrecognition and verification of a subject to establish user eligibilityprior to use.

In some embodiments, the system is used to verify subject compliance foruse of a modified risk product. In some embodiments the system comprisesa means for validating overall success of the risk mitigation productwhen used with the risk evaluation and mitigation strategies

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A method comprising: sampling, via a sensor, asample of breath of a user of an electronic vaporizer, the sensordisposed on the electronic vaporizer; generating, via the sensor, acurrent corresponding to a concentration of a gas in the sample of thebreath of the user; comparing, via electronic circuitry, thecorresponding concentration of the gas with a threshold; and enablingoperation, via the electronic circuitry, of the electronic vaporizerbased on the comparison of the corresponding concentration of the gas inthe sample of the breath of the user based on the current to thethreshold.
 2. The method of claim 1, wherein the sensor is disposed on amouthpiece of the electronic vaporizer.
 3. The method of claim 1,wherein the enabling operation of the electronic vaporizer enablesoperation when the corresponding level of the gas in the sample of thebreath of the user is below the threshold.
 4. The method of claim 3,wherein the gas comprises nitric oxide.
 5. The method of claim 4,wherein the threshold comprises a value indicative of whether the userhas asthma or chronic obstructive pulmonary disease.
 6. The method ofclaim 1, wherein the enabling operation of the electronic vaporizerenables operation when the corresponding level of the gas in the sampleof the breath of the user is above the threshold.
 7. The method of claim6, wherein the gas comprises carbon monoxide.
 8. The method of claim 7,wherein the threshold is five parts per million of carbon monoxide. 9.The method of claim 7, wherein the threshold is ten parts per million ofcarbon monoxide.
 10. The method of claim 7, wherein the thresholdcomprises a value indicative of whether the user has consumed thetobacco product within the last twenty-four hours.
 11. The method ofclaim 1, wherein the sensor comprises an electrochemical sensor.
 12. Themethod of claim 1, wherein the sensor comprises a metal oxidesemiconductor (MOS) sensor.
 13. An electronic vaporizer comprising: asensor configured to sample a user's breath and to generate a currentcorresponding to a concentration of a gas in the sample, the sensordisposed on the electronic vaporizer; and electronic circuitryconfigured to perform operations comprising: comparing the correspondingconcentration of the gas with a threshold; and enabling operation of theelectronic vaporizer based on the comparison of the correspondingconcentration of the gas in the sample of the breath of the user basedon the current to the threshold.
 14. The electronic vaporizer of claim13, wherein the sensor is disposed on a mouthpiece of the electronicvaporizer.
 15. The electronic vaporizer of claim 13, wherein theenabling operation of the electronic vaporizer enables operation whenthe corresponding level of the gas in the sample of the breath of theuser is below the threshold.
 16. The electronic vaporizer of claim 15,wherein the gas comprises nitric oxide.
 17. The electronic vaporizer ofclaim 16, wherein the threshold comprises a value indicative of whetherthe user has asthma or chronic obstructive pulmonary disease.
 18. Theelectronic vaporizer of claim 13, wherein the enabling operation of theelectronic vaporizer enables operation when the corresponding level ofthe gas in the sample of the breath of the user is above the threshold.19. The electronic vaporizer of claim 18, wherein the gas comprisescarbon monoxide.
 20. The electronic vaporizer of claim 19, wherein thethreshold is five parts per million of carbon monoxide.
 21. Theelectronic vaporizer of claim 19, wherein the threshold is ten parts permillion of carbon monoxide.
 22. The electronic vaporizer of claim 19,wherein the threshold comprises a value indicative of whether the userhas consumed the tobacco product within the last twenty-four hours. 23.The electronic vaporizer of claim 13, wherein the sensor comprises anelectrochemical sensor.
 24. The electronic vaporizer of claim 13,wherein the sensor comprises a metal oxide semiconductor (MOS) sensor.